New α‐Tetralone Galloylglucosides from the Fresh Pericarps of Juglans sigillata

Three new α‐tetralone galloylglucosides, 1 – 3 , were isolated from the fresh pericarps of Juglans sigillata (Juglandaceae), together with six known compounds. The structures of the new compounds were determined as 1,2,3,4‐tetrahydro‐7‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 1 ), (1S)‐1,2,3,4‐tetrahydro‐8‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 2 ), and 1,2,3,4‐tetrahydro‐7,8‐dihydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 3 ), respectively, on the basis of detailed spectroscopic analyses, and acidic and enzymatic hydrolysis. The antimicrobial activities of the isolated compounds 2, 4 , and 7 – 9 were evaluated.     

The complexation of rhodium(III) with acyclic diaminedithioether (DADTE) ligands

(103)Rhodium(III) complexes derived from seven acyclic tetradentate N(2)S(2) ligands (one diaminedithiol and six diaminedithioether ligands) have been synthesized and characterized. Structural variations in the ligand include the length of carbon backbone between the coordinating atoms (222; 232; 323; 333), the presence or absence of gem-dimethyl groups α to sulfur, and the nature of the organic moiety on the sulfurs (hydrogen, p-methoxybenzyl and methyl). For each ligand, the formation of cis and/or trans dichloro isomeric complexes was assessed. Two complexes have been further characterized by single crystal X-ray diffraction. Preparation of the (103)Rhodium(III) complexes was conducted and overall radiochemical yields, in vitro stability and log D(7.4) values were measured. From these studies, the ligand with the 232 chain length, gem-dimethyl groups and the methyl thioether (L4) emerged as a preferred ligand for formation of rhodium complexes with trans geometry and highest radiochemical yields.     

Structural and Spectral Analyses of 2-[(2-Benzothiazolylmethyl)thio]-benzenamine and 2-[(2-Benzothiazolylmethyl)thio]-benzenamine hydrobromide

Abstract  

2-[2-benzothiazoylmethyl)thio]-benzenamine, which was first reported in 1898, was isolated from the reaction of bromoacetyl bromide and 2-aminothiophenol [1]. The product crystallized from an aqueous methanol solution of the reaction mixture to which nickel(II) acetate had been added. 2-[(2-benzothiazolylmethyl)thio]-benzenamine crystallized in the monoclinic system, in space group C2/c, with cell dimensions of a = 27.392 (19) ?, b = 4.730 (3) ?, and c = 23.686 (16) ?, β = 122.465 (6)°, V = 2589(3) ?³, Z = 8 and refined to R = 0.0343 and R _w  = 0.0844. Crystallization from methanol yielded the product as the hydrobromide salt in the monoclinic space group Cc, with cell dimensions of a = 10.488 (3) ?, b = 33.404 (9) ?, c = 5.2578 (14) ?, β = 116.769(2)°, V = 1644.7(8) ?³, Z = 4 and refined to R = 0.0296 and R _w  = 0.0600. Mass spectral and NMR analyses confirmed that the bulk and crystalline compound were all 2-[(2-benzothiazolylmethyl)thio]-benzenamine.     

Design and synthesis of screening libraries based on the muurolane natural product scaffold

The plant-derived natural product 14-hydroxy-6,12-muuroloadien-15-oic acid (1) was identified as a unique scaffold that could be chemically elaborated to generate novel lead- or drug-like screening libraries. Prior to synthesis a virtual library was generated and prioritised based on drug-like physicochemical parameters such as log P, log D(5.5), hydrogen bond donors/acceptors, and molecular weight. The natural product scaffold (1) was isolated from the endemic Australian plant Eremophila mitchellii and then utilised in the parallel solution-phase generation of two series of analogues. The first library consisted of six semi-synthetic amide derivatives, whilst the second contained six carbamate analogues. These libraries have been evaluated for antimalarial activity using a chloroquine-sensitive Plasmodium falciparum line (3D7) and several compounds displayed low to moderate activity with IC(50) values ranging from 14 to 33 μM.     

Structural isomerism in tris-tolyl halo-phosphonium and halo-arsonium tri-halides, [(CH3C6H4)3EX][X3], (E = P, As; X = Br, I)

The group 15 ligands (o-CH(3)C(6)H(4))(3)P, (m-CH(3)C(6)H(4))(3)P, (p-CH(3)C(6)H(4))(3)P, Ph(3)As, (o-CH(3)C(6)H(4))(3)As and (p-CH(3)C(6)H(4))(3)As have been reacted with two equivalents of di-iodine or di-bromine to yield complexes of formula R(3)EX(4) (E = P, As; X = I, Br). These halogenated group 15 compounds are ionic, [R(3)EX][X(3)] consisting of halo-phosphonium or halo-arsonium cations and trihalide anions. These adducts exhibit structural isomerism and may exist either as simple 1:1 ion pairs, [R(3)EX][X(3)], isomer (A), which display a weak XX interaction between cation and anion, or as a 2:1 complex, which consists of a [{R(3)EX}(2)X(3)](+) cationic species made up of two [R(3)EX](+) cations interacting with one [X(3)](-) anion. The overall charge is balanced by a second [X(3)](-) anion. These 2:1 species also exhibit structural isomerism due to subtle differences in the connectivity of the [{R(3)EX}(2)X(3)](+) fragment, as the {R(3)EX}(+) units may either interact at the same end of the [X(3)](-) ion, to give a Y-shaped motif, isomer (B), or at opposite ends, giving a Z-shaped motif, isomer (C). The type of structural isomer formed is related to the way in which [Ar(3)EX](+) cations pack together via aryl embraces. Isomer (A) and (C) structures form chains of side-to-side, anti-parallel embracing cations. In (A) and (C) structures a square-like stacking motif of cations is observed. In contrast, isomer (B) structures feature side-to-side, parallel embracing cations, and do not exhibit the square motif.     

Forensic analysis of <Emphasis Type="Italic">Salvia divinorum</Emphasis> using multivariate statistical procedures. Part II: association of adulterated samples to <Emphasis Type="Italic">S. divinorum</Emphasis>

Salvia divinorum is a plant material that is of forensic interest due to the hallucinogenic nature of the active ingredient, salvinorin A. In this study, S. divinorum was extracted and spiked onto four different plant materials (S. divinorum, Salvia officinalis, Cannabis sativa, and Nicotiana tabacum) to simulate an adulterated sample that might be encountered in a forensic laboratory. The adulterated samples were extracted and analyzed by gas chromatography–mass spectrometry, and the resulting total ion chromatograms were subjected to a series of pretreatment procedures that were used to minimize non-chemical sources of variance in the data set. The data were then analyzed using principal components analysis (PCA) to investigate association of the adulterated extracts to unadulterated S. divinorum. While association was possible based on visual assessment of the PCA scores plot, additional procedures including Euclidean distance measurement, hierarchical cluster analysis, Student’s t tests, Wilcoxon rank-sum tests, and Pearson product moment correlation were also applied to the PCA scores to provide a statistical evaluation of the association observed. The advantages and limitations of each statistical procedure in a forensic context were compared and are presented herein.     

Approaches for ultrafast imaging of transient materials processes in the transmission electron microscope

The growing field of ultrafast materials science, aimed at exploring short-lived transient processes in materials on the microsecond to femtosecond timescales, has spawned the development of time-resolved, in situ techniques in electron microscopy capable of capturing these events. This article gives a brief overview of two principal approaches that have emerged in the past decade: the stroboscopic ultrafast electron microscope and the nanosecond-time-resolved single-shot instrument. The high time resolution is garnered through the use of advanced pulsed laser systems and a pump-probe experimental platforms using laser-driven photoemission processes to generate time-correlated electron probe pulses synchronized with laser-driven events in the specimen. Each technique has its advantages and limitations and thus is complementary in terms of the materials systems and processes that they can investigate. The stroboscopic approach can achieve atomic resolution and sub-picosecond time resolution for capturing transient events, though it is limited to highly repeatable (>10(6) cycles) materials processes, e.g., optically driven electronic phase transitions that must reset to the material's ground state within the repetition rate of the femtosecond laser. The single-shot approach can explore irreversible events in materials, but the spatial resolution is limited by electron source brightness and electron-electron interactions at nanosecond temporal resolutions and higher. The first part of the article will explain basic operating principles of the stroboscopic approach and briefly review recent applications of this technique. As the authors have pursued the development of the single-shot approach, the latter part of the review discusses its instrumentation design in detail and presents examples of materials science studies and the near-term instrumentation developments of this technique.     

Quantitation of melatonin and n‐acetylserotonin in human plasma by nanoflow LC‐MS/MS and electrospray LC‐MS/MS

Melatonin (MEL) and its chemical precursor N‐acetylserotonin (NAS) are believed to be potential biomarkers for sleep‐related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity, specificity and dynamic range needed to monitor MEL and its precursors and metabolites in small blood samples, such as those obtained from pediatric patients. In support of our ongoing study to determine the safety, tolerability and PK dosing strategies for MEL in treating insomnia in children with autism spectrum disorder, two highly sensitive LC‐MS/MS assays were developed for the quantitation of MEL and precursor NAS at pg/mL levels in small volumes of human plasma. A validated electrospray ionization (ESI) method was used to quantitate high levels of MEL in PK studies, and a validated nanospray (nESI) method was developed for quantitation of MEL and NAS at endogenous levels. In both assays, plasma samples were processed by centrifugal membrane dialysis after addition of stable isotopic internal standards, and the components were separated by either conventional LC using a Waters SymmetryShield RP18 column (2.1 × 100 mm, 3.5 µm) or on a polyimide‐coated, fused‐silica capillary self‐packed with 17 cm AquaC18 (3 µm, 125 Å). Quantitation was done using the SRM transitions m/z 233 → 174 and m/z 219 → 160 for MEL and NAS, respectively. The analytical response ratio versus concentration curves were linear for MEL (nanoflow LC: 11.7–1165 pg/mL, LC: 1165–116500 pg/mL) and for NAS (nanoflow LC: 11.0–1095 pg/mL). Copyright © 2012 John Wiley & Sons, Ltd.     

A nonpeptidic cathepsin S activity-based probe for noninvasive optical imaging of tumor-associated macrophages

Macrophage infiltration into tumors has been correlated with poor clinical outcome in multiple cancer types. Therefore, tools to image tumor-associated macrophages could be valuable for diagnosis and prognosis of cancer. Herein, we describe the synthesis and characterization of a cathepsin S-directed, quenched activity-based probe (qABP), BMV083. This probe makes use of an optimized nonpeptidic scaffold leading to enhanced in vivo properties relative to previously reported peptide-based probes. In a syngeneic breast cancer model, BMV083 provides high tumor-specific fluorescence that can be visualized using noninvasive optical imaging methods. Furthermore, analysis of probe-labeled cells demonstrates that the probe primarily targets macrophages with an M2 phenotype. Thus, BMV083 is a potential valuable in vivo reporter for tumor-associated macrophages that could greatly facilitate the future studies of macrophage function in the process of tumorigenesis.